title: Cerebrovascular dysfunction and blood-brain barrier permeability induced by oxidized LDL are prevented by apocynin and magnesium sulfate in female rats.
abstract: Oxidized low-density lipoprotein (oxLDL) is elevated during several neurologic conditions that involve cerebral edema formation, including severe preeclampsia and eclampsia; however, our understanding of its effect on the cerebral vasculature is limited. We hypothesized that oxLDL induced blood-brain barrier (BBB) disruption and changes in cerebrovascular reactivity occur through NADPH oxidase-derived superoxide. We also investigated the effect of MgSO₄ on oxLDL-induced changes in the cerebral vasculature as this is commonly used in preventing cerebral edema formation. Posterior cerebral arteries from female rats were perfused with 5 µg/mL oxLDL in rat serum with or without 50 µM apocynin or 16 mM MgSO₄ and BBB permeability and vascular reactivity were compared. oxLDL increased BBB permeability and decreased myogenic tone that were prevented by apocynin. oxLDL increased constriction to the nitric oxide synthase inhibitor nitro-L-arginine that was unaffected by apocynin. oxLDL enhanced dilation to the NO donor sodium nitroprusside that was prevented by apocynin. MgSO₄ prevented oxLDL-induced BBB permeability without affecting oxLDL-induced changes in myogenic tone. Thus, oxLDL seems to cause BBB disruption and vascular tone dysregulation through NADPH oxidase-derived superoxide. These results highlight oxLDL and NADPH oxidase as potentially important therapeutic targets in neurologic conditions that involve elevated oxLDL.
authors.affiliation: *Departments of Neurological Sciences, †Obstetrics, Gynecology and Reproductive Sciences, and ‡Pharmacology, University of Vermont College of Medicine, Burlington, VT.
authors.forename: Malou P H
authors.initials: MP
authors.lastname: Schreurs
authors.forename: Marilyn J
authors.initials: MJ
authors.lastname: Cipolla
mesh_terms: D000098:Acetophenones / Q000494:pharmacology*; D000818:Animals; D000975:Antioxidants / Q000494:pharmacology*; D001812:Blood-Brain Barrier / Q000187:drug effects*; D002561:Cerebrovascular Disorders / Q000139:chemically induced* / Q000517:prevention & control*; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005260:Female; D008077:Lipoproteins, LDL; D008278:Magnesium Sulfate / Q000494:pharmacology*; D009119:Muscle Contraction / Q000187:drug effects; D009129:Muscle Tonus / Q000187:drug effects; D009131:Muscle, Smooth, Vascular / Q000187:drug effects; D009569:Nitric Oxide / Q000502:physiology; D020030:Nitric Oxide Donors / Q000494:pharmacology; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors; D019335:Nitroarginine / Q000494:pharmacology; D009599:Nitroprusside / Q000494:pharmacology; D010539:Permeability / Q000187:drug effects; D020769:Posterior Cerebral Artery / Q000187:drug effects; D051381:Rats; D017207:Rats, Sprague-Dawley; D013481:Superoxides / Q000378:metabolism; D014664:Vasodilation / Q000187:drug effects
chemical_list: D000098:Acetophenones; D000975:Antioxidants; D004791:Enzyme Inhibitors; D008077:Lipoproteins, LDL; D020030:Nitric Oxide Donors; C099252:oxidized low density lipoprotein; D013481:Superoxides; D009599:Nitroprusside; D019335:Nitroarginine; D009569:Nitric Oxide; D008278:Magnesium Sulfate; C056165:acetovanillone; D019001:Nitric Oxide Synthase